Microscopic examination of tissue samples, particularly those obtained by biopsy, is a common method for diagnosis of disease. In particular, immunohistochemistry (IHC), a technique in which specific antibodies are used to detect expression of specific proteins in the tissue sample, is a valuable tool for diagnosis, particularly for the detection and diagnosis of cancer.
The paired box (PAX) genes are a family of cell-lineage transcription factors that may play fundamental roles during organogenesis and are regulatory proteins expressed in normal and neoplastic cells of the same lineage. PAX8 is a nephric-lineage transcription factor that may be a crucial transcription factor for organogenesis of the thyroid gland, kidney and Müllerian system. These proteins are required for cell growth and differentiation in embryonic tissues and can be expressed in adult tissues and in specific cell-lineage neoplastic tissues.
PAX8 may have been shown to be a useful marker of several cancers, particularly kidney, ovarian, endometrial, and thyroid cancers. Detection of PAX8 by anti-PAX8 antibodies, using immunohistochemistry, may have been shown to be a valuable tool for detection and diagnosis of these cancers.
Immunohistochemical detection of PAX8 expression may be advantageous for several reasons: PAX8 may be present in a high percentage of cases of these cancers; PAX8 can identify both primary and metastatic tumors of these types; and even nuclear expression of PAX8 may result in strong staining of the nucleus, which may ease interpretation and diagnosis.
Unfortunately, some known anti-PAX8 antibodies useful for immunohistochemistry may have the disadvantage that they cross-react with lymphocytes, particularly B-cells, which may frequently infiltrate into the site of a tumor. Simultaneous staining of B-cells, alongside positive staining of PAX8, can complicate analysis and even interpretation of the tissue sample. In such cases, the pathologist may have to rely on other methods (e.g., morphological differences) to discriminate B-cell staining from tumor cells. Furthermore, staining of B-cells can be a significant disadvantage in the analysis of tissue samples from lymph nodes, a common scenario when evaluating the potential of metastasis into a lymph node. Considering that lymph nodes may naturally contain large numbers of B-cells, staining a lymph node sample with one of the currently known PAX8 antibodies may result in extensive staining of B-cells and may make identification of metastatic tumor cells in the lymph node extremely difficult. A more specific anti-PAX8 antibody that does not cross-react and stain B-cells could offer a significant advantage by simplifying interpretation, resulting in clearer, more confident and even accurate diagnosis.